Support is requested for a Keystone Symposia meeting entitled Exosomes/Microvesicles: Novel Mechanisms of Cell-Cell Communication, organized by Richard A. Cerione and Xandra O. Breakefield. The meeting will be held in Keystone, Colorado from June 19-22, 2016. An emerging area of great excitement in the cell biology and pharmaceutical/biotech communities involves the release and subsequent uptake of membrane-enclosed packets of information, often referred to as extracellular vesicles. These non-traditional vesicles contain a potent array of cargo, including hundreds of proteins such as growth factors and receptors, metabolic enzymes, transcription factors and a large variety of RNA transcripts as well as DNA. Extracellular vesicles span a range of sizes from 50 nm to 1 micron and comprise a heterogenous set, including exosomes and microvesicles that appear to be generated through distinct mechanisms. Extracellular vesicles are thought to serve as a means of cell-to-cell communication and contribute to a number of disease states, including cancer and neurodegeneration, thus offering new targets for therapeutic intervention and novel possibilities for diagnostic biomarkers. However, a number of important questions need to be answered: What are the regulatory cues that determine content and release of these vesicles from donor cells? How many different types of extracellular vesicles are there and do they vary among cell types? Are there specific uptake mechanisms of vesicles into recipient cells and is the cargo functional in these cells? The time is right for a Keystone Symposia meeting that covers this exciting area and aims to bring together investigators from the cell biology and biomedical communities to present their newest findings concerning the biogenesis of extracellular vesicles, how they are shed and dock onto target cells, and the biological and disease consequences of their functions. This meeting's focus is particularly relevant to NCI given the number of connections between microvesicle/exosome function and cancer progression. For example, extracellular vesicles have been implicated in the communication between cancer cells at a primary tumor site and their immediate microenvironment, as well as in the creation of the pre-metastatic niche at secondary sites of tumor colony formation, and in tumor angiogenesis. Moreover, these vesicles are stable in tissue fluids and have the potential to serve as biomarkers, with the idea being that microvesicles/exosomes from different types of cancer cells will contain some cargo specific to those cells. Thus, microvesicles/ exosomes offer a potentially rich area for the identification of new therapeutic anti-cancer targets and diagnosti markers